Download Optimizing stroke prevention in atrial fibrillation:

EDITORIAL
Europace (2015) 17, 507–508
doi:10.1093/europace/euv041
Optimizing stroke prevention in atrial fibrillation:
better adherence and compliance from patients
and physicians leads to better outcomes
Tatjana S. Potpara1,2*, Deirdre A. Lane 3, and Gregory Y.H. Lip 1,3,4
1
School of Medicine, Belgrade University, Belgrade, Serbia; 2Cardiology Clinic, Clinical Centre of Serbia, Visegradska 26, Belgrade 11000, Serbia; 3University of Birmingham Centre for
Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, UK; and 4Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University,
Aalborg, Denmark
For adequate stroke prevention, most patients with non-valvular
atrial fibrillation (AF) would need oral anticoagulant therapy
(OAC), with either vitamin-K antagonists (VKAs) or non-vitamin-K
oral anticoagulants (NOACs).1 Once AF has been diagnosed
(which itself may be challenging2,3), the very first priority is effective
stroke prevention based on guidelines, but physicians’ adherence to
the guidelines for AF management is still suboptimal.4 – 7 Indeed,
guideline adherent therapy is associated with better outcomes.5 An
equally important step is the patient’s actual uptake of recommended
therapy, as well as good adherence and persistence to long-term
treatment, which makes the patient a key proactive part of the
process.6
Current AF guidelines mandate discussion with patients about
their values and treatment preferences.1 In order to reach an
informed decision about treatment acceptance (or refusal), AF
patients need to understand not only AF, but also the benefits
and risks of recommended therapy. In a recent study, AF patients
generally perceived moderate or severe stroke as equal to or
worse than death, respectively, and were willing to experience
4.4 major bleeds just to prevent one stroke.7
Perhaps knowledge and understanding is crucial. Given the variable knowledge levels among AF patients,8 many educational
interventions have been developed to improve their perception
of AF and understanding of treatments implemented to prevent
AF-related complications.9 Indeed, an active structured interaction between AF patients and responsible physicians or other
healthcare providers may be crucial to achieve better outcomes
in AF management.
In the current issue of Europace, Vrijens et al. nicely highlight a changing perception of relationships between patients and health providers, from a passive patient role to ‘simply follow the physician’s
instructions’ (that is, patient compliance) to an active bilateral participation in the process termed medication adherence by which the
patients take their medications as prescribed.10 As emphasized in
this article, poor adherence to medications with a narrow therapeutic range such as the VKAs11 may result in serious consequences, including increased rates of both thromboembolism and bleeding.
Compared with VKAs, the NOACs offer several advantages including fixed dosing and the lack of anticoagulant monitoring.12
At least in theory, this should facilitate medication adherence and
persistence (that is, adherence during the whole treatment period).
However, before the transition to NOACs, a careful analysis of individual patient reasons for non-adherence to VKAs is warranted,
since simply switching the patient from VKA to an NOAC might
not necessarily result in better adherence. Given the shorter halflives of NOACs, medication adherence to NOACs is even more
important compared with VKAs.12,13
In this issue of Europace, Beyer-Westendorf et al. reported prospective results from the Dresden NOAC Registry on persistence
with rivaroxaban in AF patients.14 These are some of the first ‘realworld’ prospective data on persistence to an NOAC therapy in
daily care setting, generally showing a high overall persistence to rivaroxaban, with a discontinuation rate of 15% in the first year of
treatment and a declining discontinuation thereafter (with overall
persistence of 81.5% during the median treatment duration of 544
days).
Could these results be attributed solely to once-daily dosing of rivaroxaban? The percentage of doses taken generally increases with
less frequent dosing regimens.15 As Vrijens et al. rightly point out,
once-daily dosing may require a near-perfect medication adherence
to achieve the expected clinical results whilst twice-daily dosing, due
The opinions expressed in this article are not necessarily those of the Editors of Europace or of the European Society of Cardiology.
* Corresponding author. Tel: +381 11 3616319; fax: +381 11 3616319. E-mail address: [email protected]; [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
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This editorial refers to ‘Non-vitamin K antagonist oral
anticoagulants: considerations on once- vs. twice-daily regimens and their potential impact on medication adherence’
by B. Vrijens and H. Heidbuchel, on page 514 –523.
This editorial refers to ‘Drug persistence with rivaroxaban
therapy in atrial fibrillation patients—results from the
Dresden non-interventional oral anticoagulation registry’
by J. Beyer-Westendorf et al., on page 530 –538.
508
Conflicts of interest: T.P. reports receiving grants from Pfizer
and speaker fees from Bayer, Boehringer Ingelheim and Pfizer.
G.Y.H.L. has served as a consultant for Bayer, Astellas, Merck,
Sanofi, BMS/Pfizer, Daiichi-Sankyo, Biotronik, Portola, Medtronic,
Daiichi-Sankyo and Boehringer Ingelheim and has been on the
speaker’s bureau for Bayer, BMS/Pfizer, Boehringer Ingelheim,
Daiichi-Sankyo, Medtronic and Sanofi Aventis.
References
1. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH et al. 2012
focused update of the ESC Guidelines for the management of atrial fibrillation:
an update of the 2010 ESC Guidelines for the management of atrial fibrillation.
Developed with the special contribution of the European Heart Rhythm
Association. Europace 2012;14:1385 – 413.
2. Lowres N, Neubeck L, Redfern J, Freedman SB. Screening to identify unknown atrial
fibrillation. A systematic review. Thromb Haemost 2013;110:213 –22.
3. Potpara TS, Lane DA. Diving to the foot of an iceberg: the SEARCH for undiagnosed
atrial fibrillation. Thromb Haemost 2014;112:1 –3.
4. Lip GY, Laroche C, Boriani G, Dan GA, Santini M, Kalarus Z et al. Regional differences in presentation and treatment of patients with atrial fibrillation in Europe: a
report from the EURObservational Research Programme Atrial Fibrillation
(EORP-AF) Pilot General Registry. Europace 2015;17:194 – 206.
5. Kirchhof P, Ammentorp B, Darius H, De Caterina R, Le Heuzey JY, Schilling RJ et al.
Management of atrial fibrillation in seven European countries after the publication of
the 2010 ESC Guidelines on atrial fibrillation: primary results of the PREvention oF
thromboemolic events–European Registry in Atrial Fibrillation (PREFER in AF).
Europace 2014;16:6– 14.
6. Bottoni N, Tritto M, Ricci R, Accogli M, Di Biase M, Iacopino S et al. Adherence to
guidelines for atrial fibrillation management of patients referred to cardiology
departments: Studio Italiano multicentrico sul Trattamento della Fibrillazione
Atriale (SITAF). Europace 2010;12:1070 – 7.
7. Pisters R, van Oostenbrugge RJ, Knottnerus IL, de Vos CB, Boreas A, Lodder J et al.
The likelihood of decreasing strokes in atrial fibrillation patients by strict application
of guidelines. Europace 2010;12:779 –84.
8. Potpara TS, Polovina MM, Mujovic NM et al. Patient preferences at ten years following initial diagnosis of atrial fibrillation: the Belgrade Atrial Fibrillation Study. Patient
Prefer Adherence 2013;7:835 –42.
9. Lane DA, Barker RV, Lip GY. Best practice for atrial fibrillation patient education.
Curr Pharm Des 2015;21:533 –43.
10. Vrijens B, Heidbuchel H. Non-vitamin K antagonist oral anticoagulants: considerations on once- vs. twice-daily regimens and their potential impact on medication
adherence. Europace 2015;17:514 –23.
11. De Caterina R, Husted S, Wallentin L et al. Vitamin K antagonists in heart disease:
current status and perspectives (Section III). Position paper of the ESC Working
Group on Thrombosis—Task Force on Anticoagulants in Heart Disease. Thromb
Haemost 2013;110:1087 –107.
12. Banerjee A, Lane DA, Torp-Pedersen C, Lip GY. Net clinical benefit of new oral
anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a ‘real
world’ atrial fibrillation population: a modelling analysis based on a nationwide
cohort study. Thromb Haemost 2012;107:584 –9.
13. Camm AJ, Pinto FJ, Hankey GJ, Andreotti F, Hobbs FDR. Non-vitamin K antagonist
oral anticoagulants and atrial fibrillation guidelines in practice: barriers to and strategies for optimal implementation. Europace 2015: EUPC-D-15-00066.
14. Beyer-Westendorf J, F?rster K, Ebertz F et al. Drug persistence with rivaroxaban
therapy in atrial fibrillation patients—results from the Dresden non-interventional
oral anticoagulation registry. Europace 2015;17:524–32.
15. Laliberte F, Nelson WW, Lefebvre P et al. Impact of daily dosing frequency on adherence to chronic medications among nonvalvular atrial fibrillation patients. Adv
Therapy 2012;29:675–90.
16. Friberg L, Rosenqvist M, Lip GY. Net clinical benefit of warfarin in patients with atrial
fibrillation: a report from the Swedish atrial fibrillation cohort study. Circulation 2012;
125:2298 –307.
17. Berti D, Hendriks JM, Brandes A et al. A proposal for interdisciplinary, nursecoordinated atrial fibrillation expert programmes as a way to structure daily practice.
Eur Heart J 2013;34:2725 – 30.
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to a greater continuity duration of drug action and a smaller peakto-trough plasma concentration ratio, might appear more tolerant
to occasional non-adherence– at least in theory. As estimated
pharmacokinetically, a single missed once-daily dose equals to
2– 3 consecutively missed doses from a twice-daily drug regime.10
What are the implications? Neither once-daily nor twice-daily
dosing should be automatically considered as a better option for all
AF patients, and only after a detailed assessment of individual
patient preferences the final drug choice should be made. In addition,
a structured follow-up of AF patients taking an NOAC, with interventions to improve medication adherence and sufficient patient
education are necessary to manage NOAC adherence in clinical
practice, as also suggested by Vrijens et al. 10
Of 1204 AF patients taking rivaroxaban in the Dresden registry,
39.3% previously used warfarin, and the main reason for VKA discontinuation (in 53.7% of cases) was a labile international normalized
ratio (INR), whilst rivaroxaban was mostly discontinued following
the bleeding events (30% of discontinuations), which were predominantly non-major clinically relevant bleeds.14 Importantly, .90% of
all AF patients taking rivaroxaban had high stroke risk (CHA2DS2VASc score ≥2), but after rivaroxaban discontinuation, a worrying
15.7% of patients were left without any antithrombotic therapy,
1.8% received dual antiplatelet therapy and as many as 30% of
patients were prescribed single antiplatelet therapy. Perhaps there
is the physicians misperception that antiplatelet drugs are safer
compared to OAC or the risk of recurrent bleeding with OAC
was (often erroneously) estimated to be higher than the benefit
from OAC.12,16 Thus, practitioners would also benefit from initiatives directed towards better adherence to AF guidelines.
Indeed, interdisciplinary AF expert programmes coordinated by
clinical nurse specialists may improve patient knowledge on AF therapies and the adherence of physicians to AF guideline recommendations.17 Prospective randomized trials such is the ongoing AEGEAN
(Assessment of Education and Guidance Programme for Eliquis
Adherence in Non-Valvular AF, NCT01884350), which randomizes
patients taking apixaban to usual care or with added structured education and follow-up by a virtual clinic, will facilitate the elicitation of
patient-related factors which need further management.
With such integrated approaches, AF patients are increasingly
becoming active players in optimising stroke prevention. Ultimately,
the goal is better medication adherence and improved long-term
outcomes.
Editorial